Biology subjects

Dey, B.

Publications and source records attributed to Dey, B..

13 recordsLinked to original sources

bioRxiv2026

Unveiling Gloriosine as a Dual-Acting Regulator of Glutamine Metabolism and Ferroptosis in Triple-Negative Breast Cancer: Insights from Network Pharmacology and Experimental Validation

BackgroundTNBC lacks clearly defined molecular targets, so chemotherapy remains the standard approach despite resistance, toxicity, and high relapse rates. New, less toxic therapeutic options are urgently needed. This study evaluated the anticancer potential of gloriosine, a plant-derived alkaloid known to inhibit tumor cell growth with minimal effect on normal breast cells. MethodsPutative targets of gloriosine were predicted using SwissTargetPrediction, TargetNet, and PharmMapper, then intersected with gene sets linked to TNBC and glutamine metabolism. The resulting network was characterized through protein-protein interaction mapping and Gene Ontology/KEGG enrichment analysis. Molecular docking assessed binding affinity to top targets, and predictions were validated experimentally using cell viability, colony formation, and wound-healing assays. Oxidative stress and ferroptosis were assessed via ROS (DCFDA), glutathione, and lipid peroxidation (MDA) assays, along with Western blotting and FerroOrange staining. ResultsNetwork analysis identified 100 predicted targets, 60 overlapping with TNBC/glutamine-metabolism genes; SRC, EGFR, mTOR, and HSP90AA1 emerged as hub proteins. Enrichment analysis linked this network to cancer progression, metabolic reprogramming, and resistance pathways, including central carbon metabolism and ErbB/EGFR-inhibitor resistance signaling. Docking confirmed strong gloriosine-target binding. Experimentally, gloriosine reduced cell proliferation and migration in a dose-dependent manner. Mechanistically, it suppressed glutaminolysis and induced ferroptosis, marked by increased ROS, glutathione depletion, elevated lipid peroxidation, GPX4 suppression, and intracellular iron accumulation. ConclusionsGloriosine suppresses TNBC growth via multi-target modulation and ferroptosis induction, supporting its potential as a novel anticancer candidate. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/725321v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@aaebf6org.highwire.dtl.DTLVardef@16988bforg.highwire.dtl.DTLVardef@190db4dorg.highwire.dtl.DTLVardef@12dc2fd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Flow chart of the network pharmacological and in vitro study of gloriosine C_FIG

cancer biology↗

bioRxiv2026

Modeling and optimization of a central diamond shape threefold hexagon metamaterial sensor for glioblastoma cell detection

The present study introduces a novel design and analysis of a sensor based on a terahertz metamaterial absorber (MMA) to identify Glioblastoma cell by employing microwave imaging techniques. Terahertz (THz) frequencies offer unique advantages for biomedical applications. Computer Simulation Technology (CST) employs a finite integration (FIT) approach to simulate the suggested structure in the resonant frequency (RF) range of 4.5 THz to 6 THz. The crystal structure displays three distinct absorption peaks at resonance frequencies. The MTA can absorb energy in three specific spectral bands: 4.782 THz, 5.30 THz, and 5.7319 THz. At these frequencies, the MTM achieves exceptionally high absorption, reaching 99.99%, 99.98%, and 99.68% peak absorption, respectively. The electric field (E), magnetic field (H), and surface current of the MTM are also examined. Finally, detecting Glioblastoma cells is also being investigated by analyzing the E-field H-field using microwave imaging. The suggested biosensor features a high-quality factor of 143.63, a frequency shifts per refractive index of 1.45 THz/RIU. In this study, the PCR value is measured at 0.95 at a frequency of 4.782 THz, indicating a high efficiency in polarization conversion. Polarization Conversion Ratio (PCR) quantifies the efficiency of a metamaterial in converting the polarization of an incident electromagnetic wave. Extensive simulation studies confirm the sensors capability to distinguish between healthy and cancerous cervical tissue. The suggested MMA-based sensor has numerous advantages and can be utilized for Glioblastoma cell detection.

bioengineering↗

bioRxiv2025

Multi-omics analysis uncovers differential growth kinetics of Japanese Encephalitis Virus in human and porcine macrophages

Japanese encephalitis virus (JEV), a mosquito-borne neurotropic virus, poses a significant threat to juvenile humans, while causing mild symptoms in pigs, except piglets. Pigs with high viremia are amplifier hosts, whereas humans with lower viremia are dead-end hosts. The molecular mechanisms behind the varying viremia levels in pigs and humans remain poorly understood. A comparative multi-omics study was conducted on JEV-infected macrophages, the early site of JEV replication in both species. We identified 24 key determinants potentially regulating viral growth. Functional validation of three antiviral factors - LGALS1, ssc-miR-133a-3p, and hsa-miR-3614-5p, and two proviral factors - MIF and VMP1, in macrophages showed that the upregulation of MIF and VMP1, and downregulation of ssc-miR-133a-3p, enhanced JEV replication in pigs. In contrast, the downregulation of MIF and VMP1 and upregulation of hsa-miR-3614-5p reduced JEV replication in human macrophages. These findings provide critical insights into JEV infection and its species-specific dynamics.

microbiology↗

bioRxiv2025

Identifying a novel mechanism of L-leucine uptake in Mycobacterium tuberculosis using a chemical genomic approach

Amino acid biosynthesis is vital for Mycobacterium tuberculosis (Mtb) proliferation and tuberculosis pathogenesis. However, it is not clear how amino acids are transported in Mtb, particularly the branched chain amino acids (BCAAs) that contribute to the production of the cell-wall lipid component precursors such as acetyl-CoA and propionyl-CoA. While performing the screening of an FDA-approved repurposed library of small molecule inhibitors against the auxotrophic strain Mtb mc2 6206, which lacks leuC-leuD and panC-panD genes, we identified a molecule namely semapimod, which exclusively inhibits growth of the auxotrophic strain, whereas no effect is observed against the wild-type Mtb H37Rv. Interestingly, 24 h of exposure of Mtb mc2 6206 to semapimod causes massive transcriptional reprogramming with differential expression of >450 genes associated with a myriad of metabolic activities. By performing a series of experiments, we affirm that semapimod indeed inhibits the L-leucine uptake in Mtb mc2 6206 by targeting a protein involved in the cell-wall lipid biosynthesis pathway. Remarkably, semapimod treatment of mice infected with Mtb H37Rv causes a significant reduction of bacterial load in lungs and spleen, despite showing no efficacy against the pathogenic strain in vitro. Overall findings of our study reveal that together with an endogenous pathway for L-leucine biosynthesis, a well-orchestrated machinery for its uptake is functional in Mtb which is important for intracellular survival of the TB pathogen.

microbiology↗

bioRxiv2024

Transcriptomic profiling identifies breed-specific immune signatures of Tuberculosis susceptibility in cattle

Tuberculosis (TB) remains a major chronic infectious disease in cattle, particularly challenging in India which hosts the worlds largest and most diverse cattle population farmed in close proximity to its human settlements. This study investigates the hypothesis that genetic and immune variations drive differential TB susceptibility in cattle breeds. Using comprehensive transcriptomic analyses, we examined immune responses in peripheral blood mononuclear cells (PBMCs) from Sahiwal and Sahiwal-Holstein Friesian (SHF) crossbred cattle. Responses to both the virulent Mycobacterium tuberculosis and the vaccine strain M. bovis BCG were compared. Notably, Sahiwal cattle exhibited a robust early immune response characterized by upregulation of interferon signaling, enhanced cytotoxic activity by CD8+ T and NK cells, and pronounced T cell recruitment and activation pathways compared to SHF crossbreds. PBMCs of this breed also demonstrated superior control of M. tuberculosis replication in vitro. A distinctive immune signature comprising 8 genes, including CXCL10, ISG15, CTLA4, SELL, TLR3, MYD88, IRF1, and EOMES was significantly upregulated in Sahiwal cattle PBMCs, potentially driving their reduced TB susceptibility. These findings underscore the importance of breed-specific immune profiling in devising effective TB control strategies, and could lead to targeted interventions that leverage genetic and immunological insights to mitigate TB in regions with high cattle diversity.

systems biology↗

bioRxiv2023

A bovine pulmosphere model and multiomics analyses identify a signature of early host response to Mycobacterium tuberculosis infection

Interactions between the tubercle bacilli and lung cells during the early stages of tuberculosis (TB) are crucial for disease outcomes. Conventional 2D cell culture inadequately replicates the multicellular complexity of lungs. We introduce a 3D pulmosphere model for Mycobacterium tuberculosis infection in bovine systems, demonstrating through comprehensive transcriptome and proteome analyses that these 3D structures closely replicate the diverse cell populations and abundant extracellular matrix proteins, emphasizing their similarity to the in vivo pulmonary environment. While both avirulent BCG and virulent M. tuberculosis-infected pulmospheres exhibit commonalities in the upregulation of several host signaling pathways, distinct features such as upregulation of ECM receptors, neutrophil chemotaxis, interferon signaling, and RIG-1 signaling pathways characterize the unique early response to virulent M. tuberculosis. Moreover, a signature of seven genes/proteins, including IRF1, CCL5, CXCL8, CXCL10, ICAM1, COL17A1, and CFB, emerges as indicative of the early host response to M. tuberculosis infection. Overall, this study presents a superior ex vivo multicellular bovine pulmosphere TB model, with implications for discovering disease biomarkers, enabling high-throughput drug screening, and improving TB control strategies.

systems biology↗

bioRxiv2023

Divergent evolutionary strategies preempt tissue collision in fly gastrulation

Metazoan development proceeds through a series of morphogenetic events that sculpt body plans and organ structures. In the early embryonic stages, morphogenetic processes involving growth and deformation occur concurrently. Forces generated in one tissue can thus increase mechanical stress in the neighboring tissue, potentially disrupting spatial patterning, morphological robustness, and consequently decreasing organismal fitness. How organisms evolved mechanisms to reduce or release inter-tissue stresses remains poorly understood. Here we combined phylogenetic survey across a whole insect order (Diptera), quantitative live imaging, and functional mechanical perturbation to investigate the evolution of mechanical stress management during epithelial expansions in the gastrulating fly embryos. We find that two distinct cellular mechanisms exist in Diptera to prevent the accumulation of compressive stress that can arise when the expanding head and trunk tissues collide. In Cyclorrhapha, a monophyletic dipteran subgroup including the fruit fly Drosophila melanogaster, the head-trunk boundary undergoes active out-of-plane deformation to form a transient epithelial fold, called the cephalic furrow (CF), which acts as a mechanical sink to preempt head-trunk collision. Genetic or optogenetic elimination of the CF leads to tissue buckling, yielding deleterious effects of axial distortion that likely results from unmitigated release of compressive stress. Non-cyclorrhaphan flies, by contrast, lack CF formation and instead display widespread out-of-plane division in the head, which shortens the duration of its expansion and reduces surface area increase. Reorienting head mitosis in Drosophila from in-plane to out-of-plane partially suppresses the need for epithelial out-of-plane deformation, suggesting that out-of-plane division can act as an alternative mechanical sink to prevent tissue collision. Our data suggest that programs of mechanical stress management can emerge abruptly under selective pressure of inter-tissue mechanical conflict in early embryonic development.

developmental biology↗

bioRxiv2023

Differential regulation of the proteome and phosphosproteome along the dorso-ventral axis of the early Drosophila embryo

The initially homogeneous epithelium of the early Drosophila embryo differentiates into regional subpopulations with different behaviours and physical properties that are needed for morphogenesis. The factors at top of the genetic hierarchy that control these behaviours are known, but many of their targets are not. To understand how proteins work together to mediate differential cellular activities, we studied in an unbiased manner the proteomes and phosphoproteomes of the three main cell populations along the dorso-ventral axis during gastrulation using mutant embryos that represent the different populations. We detected 6111 protein groups and 6259 phosphosites of which 3399 and 3433 respectively, were differentially regulated. The changes in phosphosite abundance did not correlate with changes in host protein abundance, showing phosphorylation to be a regulatory step during gastrulation. Hierarchical clustering of protein groups and phosphosites identified clusters that contain known fate determinants such as Doc1, Sog, Snail and Twist. The recovery of the appropriate known marker proteins in each of the different mutants we used validated the approach, but also revealed that two mutations that both interfere with the dorsal fate pathway, Toll10B and serpin27aex do this in very different manners. Diffused network analyses within each cluster point to microtubule components as one of the main groups of regulated proteins. Functional studies on the role of microtubules provide the proof of principle that microtubules have different functions in different domains along the DV axis of the embryo.

developmental biology↗

bioRxiv2023

Restriction of the growth and biofilm formation of ESKAPE pathogens by caprine gut-derived probiotic bacteria

The accelerated rise of antimicrobial resistance (AMR) poses a significant global health risk, necessitating the exploration of alternative strategies for combating pathogenic infections. Biofilm-related infections, which are unresponsive to standard antibiotics, often require the use of higher-order antimicrobials with toxic side effects and a potential for disrupting the microbiome. Probiotic therapy, with its diverse benefits and inherent safety, is emerging as a promising approach for preventing and treating various infections and as an alternative to antibiotic therapy. In this study, we isolated novel probiotic bacteria from the gut of domestic goats (Capra hircus) and evaluated their antimicrobial and antibiofilm activities against the ESKAPE group of pathogens. We performed comprehensive microbiological, biochemical, and molecular characterizations, including analysis of the 16S-rRNA gene V1-V3 region and the 16S-23S ISR region, on 20 caprine gut-derived lactic acid bacteria (LAB). Among these, six selected LABs demonstrated substantial biofilm formation in anaerobic conditions, and exhibited robust cell surface hydrophobicity and autoaggregation properties highlighting their superior enteric colonization capability. Notably, these LAB isolates exhibited broad-spectrum growth inhibitory and anti-biofilm properties against ESKAPE pathogens. Additionally, the LAB isolates were susceptible to antibiotics listed by the European Food Safety Authority (EFSA), within the prescribed Minimum Inhibitory Concentration limits, suggesting their safety as feed additives. The remarkable probiotic characteristics exhibited by the caprine gut-derived LAB isolates in this study strongly endorse their potential as compelling alternatives to antibiotics and as direct-fed microbial (DFM) feed supplements in the livestock industry, addressing the escalating need for antibiotic-free animal products.

microbiology↗

bioRxiv2023

Divergent proinflammatory immune responses associated with the differential susceptibility of cattle breeds to Tuberculosis

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines due to M. tuberculosis-indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bovine TB (bTB) prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-{gamma}), interleukin-17 (IL-17), and tank binding kinase-1 (TBK-1) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1{beta} transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to TB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.

immunology↗

bioRxiv2019

Polarity protein distribution on the metaphase furrow regulates hexagon dominated plasma membrane organization in syncytial Drosophila embryos

Epithelial cells have a polarised distribution of protein complexes on the lateral membrane and are present as a polygonal array dominated by hexagons. Metazoan embryogenesis enables the study of temporal formation of the polygonal array and mechanisms that regulate its distribution. The plasma membrane of the syncytial Drosophila blastoderm embryo is organized as a polygonal array during cortical division cycles with an apical membrane and lateral furrow in between adjacent nuclei. We find that polygonal plasma membrane organization arises in syncytial division cycle 11 and hexagon dominance occurs with increase in furrow length in cycle 12. This is coincident with DE-cadherin and Bazooka enrichment at edges and the septin, Peanut enrichment at vertices of the base of the furrow. DE-cadherin depletion leads to loss of hexagon dominance. Bazooka and Peanut depletion leads to a delay in occurrence of hexagon dominance from nuclear cycle 12 to 13. Hexagon dominance in Bazooka and Peanut mutants occurs with furrow extension and correlates with increase in DE-cadherin in syncytial cycle 13. We conclude that a change in polarity complex distribution leads to loss of furrow stability thereby changing the polygonal organization of the blastoderm embryo.\n\nHighlight Summary for TOCMetazoan embryogenesis starts with the formation of polygonal epithelial-like cells. We show that hexagon dominance in polygonal epithelial-like plasma membrane organization occurs in nuclear cycle 12 in the syncytial blastoderm Drosophila embryo. DE-cadherin and Bazooka distribution along the lateral furrow regulates this hexagon dominance.

developmental biology↗

bioRxiv2019

Cyto-architecture constrains a photoactivation induced tubulin gradient in the syncytial Drosophila embryo

Drosophila embryogenesis begins with nuclear division in a common cytoplasm forming a syncytial cell. Morphogen gradient molecules spread across nucleo-cytoplasmic domains to pattern the body axis of the syncytial embryo. The diffusion of molecules across the syncytial nucleo-cytoplasmic domains is potentially constrained by association with the components of cellular architecture, however the extent of restriction has not been examined so far. Here we use photoactivation (PA) to generate a source of cytoplasmic or cytoskeletal molecules in order to monitor the kinetics of their spread in the syncytial Drosophila embryo. Photoactivated PA-GFP and PA-GFP-Tubulin within a fixed anterior area diffused along the antero-posterior axis. These molecules were enriched in cortical cytoplasm above the yolk-filled center suggesting that the cortical cytoplasm is phase separated from the yolk-filled center. The length scales of diffusion were extracted using exponential fits under steady state assumptions. PA-GFP spread to greater distance as compared to PA-GFP-Tubulin. Both gradients were steeper and more restricted when generated in the center of the embryo probably due to a higher density of nucleo-cytoplasmic domains. The length scale of diffusion for PA-GFP-Tubulin gradient increased in mutant embryos containing short plasma membrane furrows and disrupted tubulin cytoskeleton. The PA-GFP gradient shape was unaffected by cyto-architecture perturbation. Taken together, these data show that PA-GFP-Tubulin gradient is largely restricted by its incorporation in the microtubule network and intact plasma membrane furrows. This photoactivation based analysis of protein spread across allows for interpretation of the dependence of gradient formation on the syncytial cyto-architecture.

developmental biology↗

bioRxiv2018

BCG overexpressing an endogenous STING agonist provides enhanced protection against pulmonary tuberculosis

Stimulator of interferon genes (STING) has emerged as a key signaling receptor that induces proinflammatory cytokines, and small molecule STING agonists are being developed as anticancer and antiviral agents. Here we report a strategy of delivering a STING agonist from within live BCG. We generated a recombinant BCG (BCG-disA-OE) that overexpresses the endogenous mycobacterial diadenylate cyclase gene and releases high levels of the STING agonist c-di-AMP. In macrophages BCG-disA-OE elicited statistically significantly stronger TNF-, IL-6, IL-1{beta}, IRF3, and IFN-{beta} levels than BCG-WT. In a 24-week guinea pig vaccination-Mtb challenge model, BCG-disA-OE reduced lung weights, pathology scores, and Mtb CFU counts in lungs by 28% (p<0.05), 34%, and 2.0 log10 CFU units (p < 0.5) compared with BCG-WT, respectively. Overproduction of the STING agonist c-di-AMP significantly enhanced the protective efficacy of BCG against pulmonary and extrapulmonary tuberculosis. Our findings support the development of BCG-vectored STING agonists as a TB vaccine strategy.

microbiology↗